Two trends have become significant in driving the delivery of medical treatments: 1) treatments, be they drugs, energy or surgery, are moving towards local and focal delivery, and 2) treatments are being tailored and optimized for each patient based on their specific anatomy, physiology and disease features. These directions both are designed to minimize the likelihood of adverse effects from the therapies as well as provide a more patient-specific treatment, which may improve disease-free survival rates and/or improve disease recurrence.
These trends began in surgery where large, open surgical procedures have been and continue to be replaced by minimally-invasive procedures and endoscopic procedures. Drug therapies are moving toward more localized delivery as well, such as treatments that are placed directly at or near the treatment site (e.g., drug eluting stents and Gliadel wafers for brain tumors). Until recently, the desire to do the same in radiation therapy has been hampered by inadequate technology for focused delivery. However, significant progress in local radiation delivery has been accomplished in the brachytherapy subspecialty of radiation oncology, most notably in prostate and breast cancer patients. In breast brachytherapy, the radiation source is temporarily inserted into a temporarily placed catheter inside the breast and the appropriated dose of radiation is delivered from the “inside out”. This approach has gained popularity because it offers a number of benefits to patients undergoing treatment for breast cancer including delivery in a shorter timeframe and delivery to a smaller volume of the breast tissue (i.e., accelerated and smaller volume treatments).
External beam radiation therapy (EBRT) is one of the most common adjuvant therapies for cancer patients in the U.S., with chemotherapy being the other one. EBRT is delivered to cancer patients as either the first line of therapy (for non-resected cancers) or as a means of maximizing local control of the cancer following surgical removal of the tumor. In EBRT, one or more beams of high energy x-rays are aimed at the part of the body needing radiotherapy. A linear accelerator (often called a linac) produces the beams and has a collimator that helps to shape the beams as they exit the linac. It is very common for a tumor to be treated using two or more beams, each of which is delivered from different directions around the tumor, and that all intersect at the tumor site. In this manner, the tissue surrounding the target can be exposed to lower radiation doses than the sum of the treatment beams yields at the tumor target. The tumor target volume is delineated by the radiation oncologist using CT scans (or other imaging methods such as ultrasound or MRI) of the patient. The tumor target volume and radiation dose prescription parameters are entered into a treatment planning computer. Treatment planning software (TPS) then produces a plan showing how many beams are needed to achieve the radiation oncologist's prescription dose, as well as the size and shape of each beam.
The complete course of EBRT is divided (called fractionation) into numerous small, discrete treatments called fractions. A typical prescribed dose of 60 Gray (Gy) is fractionated into 30 daily treatments of 2 Gy per day. During a fraction, the treatment beam may be “on” for .about.1 minute. Thus, the full radiotherapy treatment takes about 6 weeks (5 fractions per week) to complete.
Historically, EBRT has been practiced exactly as has chemotherapy, namely, the radiation doses delivered to the patient are limited only by the tolerance of normal tissues surrounding the site to be treated. Hence, often, the radiation therapy is continued until side-effects become intolerable for the patient. Effectively, radiation therapy has been a “radiate until the patient can't take it anymore” type of treatment. The target volume, in which it is desired to deliver essentially 100% of the prescribed radiation dose, has historically been defined as the tumor (the gross tumor volume, or GTV) plus a surrounding volume of tissue margin that may harbor remaining microscopic tumor cell foci (the clinical target volume, or CTV). Another margin of surrounding normal tissue is added to the CTV to account for errors in positioning of the patient for therapy and movement of the tumor site both during a fraction and between fractions. Chest and upper abdomen radiation therapy (e.g., lung cancer and pancreatic cancer) are two examples where large margins are needed to make sure that the changes in tissue position during respiration do not result in the target leaving the beam during some portion of the fraction delivery.
In the last few years, the treatment planning software and linear accelerator technology have dramatically improved in their ability to shape the radiation therapy beams to better avoid nearby sensitive structures. The latest treatment planning software allows the radiation oncologist and medical physicist to define the volume of tissue to be treated using CT scans and provide therapy constraints (e.g., minimum radiation dose inside the target volume, maximum radiation dose to structures nearby target volume). The software then automatically computes the beam angles and shapes in a process called inverse treatment planning. This process can be even further refined using a technique called Intensity Modulated Radiation Therapy (IMRT) which shapes the beam of radiation. Another feature of the newer linacs is a type of radiographic (and/or ultrasonic) imaging that is used to better position the patient and his/her tumor for more accurate targeting of the treatment beams. This latter method is called Image Guided Radiation Therapy, or IGRT.
Both IMRT and IGRT techniques use numerous, smaller and more precisely shaped beams that intersect at the target volume. IGRT differs from IMRT in at least one important aspect—imaging prior to each fraction is used to reduce positioning errors and make sure the treatment beam is properly targeted. Typically, IGRT uses bony anatomy (e.g., pelvic bones for prostate patients) for radiographic targeting and soft tissue interfaces (e.g., prostatic capsule and bladder wall) for ultrasound targeting. Rarely, implanted radio-opaque markers (e.g., Visi-Coil) have been used to facilitate targeting for IGRT. However, using a definitive target in order to define the limits or margins of treatment area has not been accomplished. In the treatment of breast cancer specifically, some clinicians have attempted to help delineate the margins of the lumpectomy cavity by using radio-opaque markers such as surgical clips placed at the time of surgery. This, in theory, would help the radiation oncologist in treatment planning, however, often these clips are inaccurate in their placement and have a tendency to migrate postoperatively due to healing and scarring. In addition, these markers have not been used for targeting in the newer delivery methods, such as for each fraction or each beam of every fraction as is done in IGRT.
IMRT uses a special type of collimator, a multi-leaf collimator (MLC) that changes the shape of the beam during each fraction to modulate or “sculpt” the radiation dose to more closely fit the actual target volume shape in three dimensions. Linacs with MLCs can control the size and shape of the beam to within a few millimeters accuracy.
IGRT is a relatively new option on linacs. New linacs are being sold today that have on-board imaging capability via mega-voltage (MV) or kilo-voltage (KV) x-rays/fluoroscopy. The on-board imaging capability can also be retrofitted to existing linacs. On-board imaging is a technical capability that has been introduced into the newest linac product lines by all the major linac manufacturers (e.g., Varian Medical Systems, Elekta, Tomotherapy, Accuray and Siemens). While the technology made by these companies provides the possibility of performing better targeting for external beam radiation therapy, the targets (e.g., bony anatomy) are inadequate in order to achieve a precise and accurate target region for treatment.
As described above, targeting the external beam radiation therapy accurately requires one to point out the target using fiducial markers having different radiographic properties than that of surrounding tissue (e.g., bone, and soft tissue). To date, this has been accomplished using radio-opaque markers (e.g., permanently implanted foreign bodies). Alternatively, Patrick and Stubbs described a device and method for shaping and targeting EBRT using a temporarily implanted balloon catheter (U.S. Pat. No. 7,524,274). This device and method required implantation of a foreign body whose removal necessitated a second medical procedure. There is clinical evidence suggesting that the implantation and irradiation of an area of the breast surrounding an implanted balloon can result in long-standing complications such as persistent seroma (collection of fluid within the breast that may become infected).
Hence, the need exists for a better device and method for positioning the target volume and providing a visual target for the external beam treatments, without requiring subsequent removal.